Efficacy,Tolerability,Safety of Temsirolimus in Women With Platinum-refractory Ovarian Carcinoma or Advanced Endometrial Carcinoma

Ovarian Neoplasms Clinical Trial

Official title:

Activity, Tolerability, Safety of Temsirolimus in Women With Ovarian Cancer Who Progressed During Previous Platinum Chemotherapy or Within 6 Months After Therapy or Advanced Endometrial Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01460979
• Other study ID #: AGO-GYN 8
• Status: Completed
• Phase: Phase 2
• First received: October 25, 2011
• Last updated: February 26, 2016
• Start date: October 2011
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: AGO Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the activity, tolerability and safety of Temsirolimus in women with ovarian cancer who progressed during the previous platinum chemotherapy alternatively within 6 months from completion of therapy or advanced endometrial carcinoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: November 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women = 18 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status = 2

• Before performance of study specific actions or assessment the patient has to be informed, has signed the written consent and is willing to follow the requirements concerning treatment and follow-up.Comment: Procedures which are according to common clinical routine and having been performed before having given written informed consent may be used for the purpose of screening procedures or initial medical assessment as long as these procedures follow the protocol.

• Required: negative pregnancy test in fertile women

Stratum A - Ovarian Cancer:

• Histologically confirmed Ovarian Cancer

• Platin-refractory relapsed disease: progression within a platin-based chemotherapy or within 6 months after completion of a platin-based chemotherapy

• Prior treatment with a taxane-based scheme

• minimum of one measurable or non-measurable tumor lesion(according to RECIST 1.1 criteria)

• Not more than 2 previous chemotherapies or cytostatic therapies (i.e. monoclonal antibodies, cytokines, signal transduction inhibitors)

Stratum B - Endometrian Cancer:

• Histologically confirmed Endometrian Cancer

• Advanced (International Federation of Gynaecology and Obstetrics (FIGO) III or IV) or relapsed diseases not amenable to potentially curative treatment with local surgery and/or radiation therapy

• Prior endocrine therapy is allowed

• Prior adjuvant chemotherapy is allowed

• Minimum of one measurable or non-measurable tumor lesion(according to RECIST 1.1 criteria)

Exclusion Criteria:

• ECOG > 2

• Prior therapy with mammalian target of rapamycin (mTOR) -Inhibitor

• Cytostatic therapy (i.e. monoclonal antibodies, cytokines, signal transduction inhibitors), cytotoxical chemotherapy or endocrine therapy or radiation at the same time

• Current or recent treatment with another study drug and/or participation in another clinical study within 28 days prior to first dose of study treatment

• Chemotherapy or cytostatic therapy (i.e. monoclonal antibodies, cytokines, signal transduction inhibitors) or radiation within 28 days prior to start of study treatment

• Known or supposed hypersensitivity compared to study medication

• Acute or chronical infection

• Second malignancy which influences the prognosis of the patient

• Inadequate renal function (Creatinin > 1.5 x Upper Limit of Normal (ULN))

• Inadequate liver function (aspartate transaminase (AST), alanine transaminase (ALT), gamma-Glutamyl transpeptidase (GGT) > 2.5 x ULN or > 5.0 x ULN in the presence of liver metastasis; Bilirubin > 1.5 x ULN)

• Platelets < 100.000 /µl; Absolute Neutrophil Count (ANC) < 1.500 /µl

• Cachectic patients with weight < 45kg

• Patients who need parenteral nutrition

• Patients with ileus within the last 28 days

• One of the following diseases within 12 months prior to first study treatment:

myocardial infarction, severe/unstable angina, bypass surgery of the coronar- or peripheral vessels, symptomatic heart insufficiency, cerebrovascular insult, transient ischemic attack (TIA), pulmonary embolism, deep venous thrombosis, other thromboembolic events

• Current treatment with Cytochrome P450 3A4 (CYP3A4) -Inhibitors (i.e. protease inhibitors, antimycotics, calcium channel blocker, macrolide antibiotics, Cimetidine) or -inductors (i.e. Carbamazepin, Phenobarbital, Phenytoin, Rifampicin, amber)

• Uncontrolled hypertension (> 150/100 mmHg despite optimal medicinal treatment)

• Current cardiac arrhythmias (Common Terminology Criteria for Adverse Events of National Cancer Institute (NCI CTCAE) grade = 2), atrial fibrillation, prolongation of QTc > 470 msec

• Left ventricular ejection fraction (LVEF) = 50% defined by echocardiogram

• NCI CTCAE grade 3 hemorrhage within 4 weeks prior to beginning of treatment

• Symptoms which indicate brain metastases, spinal cord compression or give new indications for brain- or leptomeningeal metastases

• Human immunodeficiency virus (HIV) positive or manifested Acquired Immune Deficiency Syndrome (AIDS-disease)

• Patients with other severe diseases who represent an inadequate risk for study participation

Applicable only for patients with no hysterectomy and/or bilateral adnexectomy prior to start of study.

• lactation

• potential fertile women without adequate contraception (potential fertile women must use one of the following adequate contraception: complete abstinence, intrauterine spiral or another method with a failure quote < 1% per year)

• life expectancy < 3 months

• neurological or psychiatric diseases or drugs or alcohol abuse which suppose no adequate comprehension and consequently no effective consent to study participation or no acceptable compliance during the study

• predictable problems with the compliance to appointments for examinations

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Neoplasms
• Genital Diseases, Female
• Neoplasms
• Ovarian Diseases
• Ovarian Neoplasms

Intervention

Drug:
• Temsirolimus
25mg weekly intravenous until progression

Locations

Country	Name	City	State
Germany	Charité, Campus Virchow Klinikum	Berlin
Germany	GYNAEKOLOGICUM Bremen	Bremen
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Universität Erlangen-Nürnberg	Erlangen	Bayern
Germany	Kliniken Essen Mitte, Evang. Huyssens Stiftung/Knappschaft GmbH	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Klinikum der J. W. Goethe-Universität	Frankfurt am Main	Hessen
Germany	Klinikum Göttingen, Georg-August-Universität	Göttingen	Niedersachsen
Germany	Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität	Greifswald	Mecklenburg Vorpommern
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Gynäkologisch-onkologische Praxis	Hannover	Niedersachsen
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel	Schleswig-Holstein
Germany	Universitätsklinikum Gießen-Marburg, Standort Marburg	Marburg	Hessen
Germany	Klinikum rechts der Isar der Technischen Universität	München	Bayern
Germany	Klinikum Offenbach	Offenbach	Hessen
Germany	Städt. Klinikum Solingen gGmbH	Solingen	Nordrhein-Westfalen
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
AGO Study Group

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival		after 4 months for ovarian cancer and 6 months for endometrial carcinoma after study entry	No
Secondary	rate and duration of stable diseases according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and Gynecologic Cancer Intergroup (GCIG)-criteria for ovarian cancer		every 8 weeks until progression	No
Secondary	progression-free survival according to RECIST 1.1 and cancer antigen 125 (CA 125) (for ovarian cancer) (biological progression-free survival (PFSbio))		every 8 weeks until progression	No
Secondary	overall survival		weekly until progression; thereafter every 8 weeks	No
Secondary	safety and toxicity, i.e. type, frequency, severity and duration of adverse reactions		weekly until progression; thereafter every 8 weeks	Yes
Secondary	quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) questionaires "QLQ C30", "QLQ OV28" and "QLQ-EN24"		every 8 weeks	No
Secondary	rate and duration of stable diseases according to RECIST-criteria for endometrial cancer		every 8 weeks until progression	No

External Links

•   Final publication